Gastroprotective Effect of Sumatriptan Against Indomethacin-, Stress- and Ethanol-Induced Gastric Damage in Male Rats: Possible Modulatory Role of 5-Hydroxytryptamine 1B/1D Receptors and Pro-Inflammatory Cytokines Publisher Pubmed



Ostovaneh A^{1, 2, 3} ; Eslami F^{1, 2, 3, 4} ; Rahimi N^{1, 2} ; Dejban P^{1, 2, 5} ; Shafaroodi H^{1, 2} ; Abbasi A⁶ ; Shahsavarhaghighi S^{1, 2} ; Dehpour AR^{1, 2} Show Affiliations
Source: Basic and Clinical Pharmacology and Toxicology Published:2023

Abstract

The current study was aimed to investigate the beneficial effect of sumatriptan, a 5-hydroxytryptamine 1B/1D (5HT1B/1D) receptor agonist, on gastric ulcer in rats via stimulating 5HT1B/1D receptors and suppressing pro-inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5 ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1 mg/kg, i.p) 30 min before gastric ulcer induction. GR-127935 (0.01 mg/kg, i.p, a selective 5HT1B/1D antagonist) was administered 30 min before sumatriptan (0.1 mg/kg) injection. Macroscopic assessments (J-score), ELISA analysis of tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J-score, TNF-α, IL-1β and microscopic features. Sumatriptan (0.1 mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J-score, TNF-α, IL-1β and microscopic lesions. Concurrent administration of GR-127935 (0.01 mg/kg) with sumatriptan (0.1 mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin-, WRS- and ethanol-induced gastric damage in rats via the possible involvement of the 5HT1B/1D receptors. © 2023 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.